Certain techniques in molecular biology, chemistry and other disciplines require the processing of many samples in precisely the same way. Such processing might be required, for example, as part of a screening process, a statistical analysis, or a large-scale assay project.
To expedite the processing of multiple samples simultaneously, various laboratory instrument manufacturers make available so-called microwell strips and microwell arrays. (collectively, "microplates"). Microplates are typically formed from a chemically inert plastic and provide a number of small wells for holding material or liquid samples.
Microplates are available in various configurations, for example, eight well, ninety six well, and 384 well arrays. Microwells are also available in strips, or rows, which may be assembled in groups to provide arrays. Microwell strips and plates of this type are manufactured and sold by a number of companies, including Fisher Scientific of Atlanta, Ga. The outer dimensions of microwell array plates are more or less standardized from manufacturer to manufacturer; however, the individual microwells, usually cylindrical in cross-section, are typically provided with different bottom geometries, including U-shaped, V-shaped, and flat.
Microplate arrays provide a convenient vehicle for processing a large number of samples in parallel. For example, these microplate supply companies sell multichannel pipetters specifically adapted for placing a precise amount of material in multiple wells at the same time. Indeed, specialized instruments are now available, such as a stepping chemical assay machine, which automatically process the samples in all of the wells of a microplate.
Often times, particular chemical processes require some sort of heating. The traditional methods to heat microplates to a desired temperature are floating them on water in a constant temperature bath, or placing them on a rack in a gravity or convection incubator. In each of these methods, the heat transfer medium, be it water or air., can be easily held at the desired temperature, and thus these might appear to be satisfactory methods.
Unfortunately, since the wells situated on the periphery of the microplate have more surface area in contact with the water or circulating air than the inner wells, the peripheral wells will heat faster than the inner wells. This phenomenon, known as an "edge effect", can cause errors in certain processes. In the case of diagnostic tests, for example, which can be very temperature sensitive, these edge effects may sometimes completely, mask test results.
Some manufacturers have developed products specifically targeted at heating microplates. For example, Techne, Inc., of Princeton, N.J., has resorted to manufacturing their own special thin-walled plates and precisely machined heater platens that exactly match the geometry of the plates. Techne's heaters do not permit the use of plates manufactured by other companies or with different well configurations, however.
Lab-Line Instruments, Inc. of Melrose Park, Ill., has introduced a heater consisting of a machined aluminum block having a rectangular milled pocket in which a microwell plate can be placed. Upon heating the block, the surrounding air is heated, which in turn heats the microplate. The air gap between the heated block and the microplate results in extremely slow heating of such that it may take tens of minutes for the microplate to thermally stabilize. Even then, the microplate may never reach a temperature approaching the temperature of the block. In addition, the outer peripheral microwells present a larger surface area to the heated air than the inner microwells, which results in uneven heating.
As previously mentioned, the microplates from different manufacturers typically do not have uniform geometries, apart from the size and spacing of the wells. For example, they may have U-shaped, V-shaped, or flat bottoms, and may also have peripheral frame members, flanges, interstitial webbing, or other geometric differences.
In addition, although known microplate heaters do typically have a feedback control circuit of some type to regulate the temperature of the heat source, no capability is provided for determining the temperature of the contents of the wells themselves. As a result, it is often difficult to determine the precise temperature to which the wells have been heated.
It thus has heretofore not been possible to design an apparatus which accurately and uniformly heats all of the wells in microplates of differing geometries quickly and at the same rate.